Emerging Bipolar Therapies

Researchers around the world currently are exploring a wide range of possible new treatments for bipolar disorder.

Bipolar disorder, formerly called manic-depression, involves episodes of extreme mood disturbance ranging from deep depression to unrestrained mania. It affects an estimated four percent of the US population. Sufferers typically alternate between these extreme states, with normal mood states in-between.

Lithium, a central treatment of bipolar disorder, was discovered more than 50 years ago. Since that time, some additional medications have also been approved and are successfully helping people with bipolar disorder. Lamictal, an anticonvulsant originally approved for the treatment of convulsive disorders such as epilepsy, was approved by the FDA for bipolar treatment in 2003. Lamictal is particularly helpful for the depression side.

Abilify, a drug that was originally approved to treat schizophrenia, was approved for use in the treatment of bipolar disorder in 2005.

A range of other drugs have been tried with limited success. Sodium valproate (Depakote in the United Statess), an anticonvulsant, often is used to stabilize mood. Certain antipsychotic medications, including chlorpromazine (Thorazine in the United States), also are used for agitation in acute manic episodes. But antidepressants usually are ineffective for the depression stage of bipolar disorder.

A 2006 study found that only half of patients remained well two years after starting treatment. So scientists remain on the lookout for improved therapies for the mood swings of bipolar disorder.

Dr. Husseini Manji of the National Institute of Mental Health (NIMH) in Bethesda, Md., explains that current medications for bipolar disorder “certainly reduce symptoms but don’t do a good enough job. Many patients are helped, but they’re not well.” Dr. Andrea Fagiolini of the University of Pittsburgh adds: “What’s more, many patients can’t tolerate current bipolar medications because of side-effects like weight gain, sleepiness, tremor, and the sense of feeling ‘drugged’.”

Recently, researchers from NIMH have investigated the use of an anti-seasickness drug called scopolamine. In a study of 18 patients with bipolar disorder or major depressive disorder, Drs. Maura Furey and Wayne Drevets found that “rapid, robust antidepressant responses to scopolamine occurred in currently depressed patients who predominantly had poor prognoses.”

“In many cases that improvement persisted for weeks or even months,” Dr. Drevets said. He now is experimenting with scopolamine in patch form. The experts hit upon this effect of scopolamine when testing the drug for its effects on memory and attention.

Another possible new treatment also was discovered by accident. In late 2003, scientists at McLean Hospital in Belmont, Mass. noticed that depressed bipolar patients improved following brain scans called echo-planar magnetic resonance spectroscopic imaging (EP-MRSI). “Several subjects finished the EP-MRSI exam with obvious mood improvement,” they report.

Researchers carried out a study comparing EP-MRSI against standard magnetic resonance imaging (MRI) scans. Seventy-seven percent of patients showed an improvement on a structured mood rating scale following EP-MRSI, compared with 30 percent with MRI. The researchers suggest the benefit comes from specific electric fields induced by the scan, and added that patients who were not on medication fared even better.

Attempts now are being made at NIMH to incorporate scanning into a possible treatment. Another type of scan, transcranial magnetic stimulation, is also being studied.

Riluzole, a drug often used for Lou Gehrig’s disease, also is a potential candidate for bipolar disorder therapy. Riluzole has been shown to have antidepressant properties in a number of recent studies of mood and anxiety disorders.

Riluzole was tested for bipolar depression by Dr. Husseini Manji and colleagues. They gave the drug to 14 acutely depressed bipolar patients alongside lithium for eight weeks. A significant improvement was found, with no evidence of a switch into mania. “These results suggest that riluzole might indeed have antidepressant efficacy in subjects with bipolar depression,” say the team.

Dr. Manji also is looking at the effectiveness of tamoxifen, a breast cancer drug, for bipolar disorder. His recent findings suggest that it rapidly reduces mania. However, he is searching for another drug with similar action, as tamoxifen is linked to possible long term side-effects at the high doses required to treat mania. But the knowledge that tamoxifen is beneficial helps towards a better understanding of the condition. “We’re close to answering some very fundamental and important questions about the illness,” commented Dr. Manji.

Current advances in DNA research allow experts access to the genetic secrets of bipolar disorder. The technology to scan entire genomes already has highlighted several genetic variants linked to bipolar disorder.

A study from August 2007 presents “the largest database of phenotypic variables yet assembled for bipolar disorder.” Researchers from Johns Hopkins School of Medicine in Baltimore, Md. said the data is reliable enough to “detect even modest genetic effects in bipolar disorder.”